| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subfoveal choroidal neovascularization secondary to Age-Related Macular Degeneration (AMD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Subfoveal choroidal neovascularization secondary to Age-Related Macular Degeneration (AMD) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10071129 |
| E.1.2 | Term | Neovascular age-related macular degeneration |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10067791 |
| E.1.2 | Term | Wet macular degeneration |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the safety and biomarker responses of various regimens of Fovista® when administered in combination with anti-VEGF agents, in treatment naïve and treatment experienced neovascular AMD subjects. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Ophthalmic Inclusion Criteria:
The following inclusion criteria apply to the study eye:
- Best corrected visual acuity in the study eye between 20/40 and 20/200, inclusive. The VA must be re-confirmed at Day 1 prior to randomization.
- Total area of the lesion (including blood, neovascularization, and scar/atrophy) must be ≤ 9 disc areas (DA)
- Presence of subfoveal "Active CNV". "Active CNV” is defined as presence of fluorescein leakage consistent with choroidal neovascularization.
- Sub or intraretinal fluid in the anatomic fovea by OCT
- Clear ocular media and adequate pupillary dilatation to allow collection of fundus photographs and fluorescein angiograms of a sufficient quality to be analyzed by the central reading center.
- Intraocular pressure (IOP) of 21 mmHg or less
- Treatment naïve subjects or treatment experienced subjects which is defined as subjects with 2 prior sequential monthly doses of intravitreal anti-VEGF therapy given within the past 12 weeks. For treatment experienced subjects, there must be a VA change of ≤ 0 letters per Snellen VA score since the last anti-VEGF injection.
General Inclusion Criteria:
- Subjects of either gender aged ≥50 years.
- Women must agree to be using two forms of effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile; if of child-bearing potential, a serum pregnancy test must be performed within 14 days prior to the first injection with a negative result. The two forms of effective contraception must be implemented during the trial and for at least 60 days following the last dose of test medication.
- Provide written informed consent.
- Ability to comply with study and follow-up procedures and return for all trial visits. |
|
| E.4 | Principal exclusion criteria |
Ophthalmic Exclusion Criteria:
- Intravitreal treatment (including intravitreal corticosteroids) in the study eye prior to the Day 1 visit, regardless of indication, with the exception of two prior anti-VEGF injections for the Treatment Experienced cohort.
- Subjects with atrophy or scar within 1 disc area (DA) of the center of the fovea are excluded.
- Presence of significant serous pigment epithelial detachments (PEDs), such as large PEDs that constitute greater than 50% of the total lesion or have a vertical height of ≥ 600 μm.
- Presence of pure PED without subretinal hyper-reflective material.
- Presence of pigment epithelial tears or rips.
- Presence of intraocular inflammation, significant epiretinal membrane (causing distortion of macular anatomy and/or opacification), significant vitreomacular traction (causing distortion of macular anatomy), macular hole (full or partial thickness) or vitreous hemorrhage.
- Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is allowed if it occurred as a result of YAG laser posterior capsulotomy in association with prior posterior chamber IOL implantation.
- History of idiopathic or autoimmune-associated uveitis in either eye.
- Significant media opacities, including cataract, which may interfere with visual acuity assessment or fundus photography evaluation of the study eye (i.e. foveal atrophy, fibrosis, etc.).
- Significant likelihood of requiring cataract surgery in the study eye in the next 12 months.
- Presence of other causes of choroidal neovascularization, including pathologic myopia (spherical equivalent of -8 diopters or more, or axial length of 25mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis.
- Non-pharmacologic treatment (intraocular surgery or thermal laser) within three (3) months of trial entry.
- Prior thermal laser in the macular region, regardless of indication.
- Ocular or periocular infection in the past twelve (12) weeks.
- History of any of the following conditions or procedures in the study eye: rhegmatogenous retinal detachment, pars plana vitrectomy, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, or corneal transplant.
- Previous therapeutic radiation in the region of the study eye.
General Exclusion Criteria:
- Any of the following underlying conditions or diseases including:
• A definitive diagnosis of diabetes mellitus or diabetic retinopathy (regardless of HbA1c level)
• HbA1c value of ≥6.5% (If the HbA1c value is ≥ 6.5% and ≤ 6.9%, and the patient has no signs or symptoms of diabetes mellitus, has a normal creatinine, has no diabetic retinopathy and no glycosuria, then the patient may have an oral glucose tolerance test (OGTT) at the discretion of the investigator. If the 2-hour glucose value on OGTT is <200 mg/dL (<11.1mmol/L), then the patient may be enrolled.)
• History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
• History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 18.5), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrythmias requiring ongoing treatment.
• Stroke (within 12 months of trial entry).
• Any major surgical procedure within one month of trial entry.
- Any treatment with an investigational agent in the 60 days prior to randomization for any condition.
- Known serious allergies to the fluorescein dye or indocyanine green used in angiography (mild allergy amenable to treatment is allowable), or iodine, or to the components or formulation of either Fovista®, Avastin®, Lucentis®, Eylea®. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Biomarker Imaging Endpoints:
Modalities: (Fluorescein Angiography (FA), Indocyanine Green Angiography (ICGA), Optical Coherence Tomography (OCT), Optical Coherence Tomography Angiography (OCTA)
- CNV and/or CNV complex analysis with respect to area and/or volume and/or flow
Safety Endpoints:
- Severe Visual Acuity Loss (Proportion of subjects with >15 letter loss at Months 12 and 18)
- Ophthalmic Adverse Events (AEs)
- Systemic Adverse Events (AEs)
- Laboratory data (blood: hematology, renal function, hepatic function, and electrolytes) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Following Month 0-8, 10-14 and 16-18 visits. |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 8 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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